Submissions for variant NM_000289.6(PFKM):c.116G>A (p.Arg39Gln)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003062509	SCV003440520	likely pathogenic	Glycogen storage disease, type VII	2024-01-25	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 39 of the PFKM protein (p.Arg39Gln). This variant is present in population databases (rs121918193, gnomAD 0.02%). This missense change has been observed in individual(s) with glycogen storage disease type VII (PMID: 27066546). ClinVar contains an entry for this variant (Variation ID: 2137355). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PFKM protein function with a positive predictive value of 80%. This variant disrupts the p.Arg39 amino acid residue in PFKM. Other variant(s) that disrupt this residue have been observed in individuals with PFKM-related conditions (PMID: 7513946, 8037209), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Baylor Genetics	RCV003062509	SCV004203954	likely pathogenic	Glycogen storage disease, type VII	2024-02-23	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV004790329	SCV005414076	likely pathogenic	not provided	2023-08-09	criteria provided, single submitter	clinical testing	PP1, PP3, PP4, PM2_moderate, PM5